Effects of lithium on platelet membrane phosphoinositides in bipolar disorder patients: a pilot study

Rationale: In vitro and in vivo animal studies suggest that the intracellular phosphatidylinositol (PI) pathway is an important target for the effects of lithium. Objectives: We conducted a preliminary study to examine the in vivo effects of lithium treatment on platelet membrane phosphoinositides in bipolar disorder subjects, in an attempt to examine further the hypothesis that lithium has significant in vivo effects on the PI pathway in these patients. Method's: We quantitated PI, phosphatidylinositol-4-phosphate (PIP). and phospharidylinositol-4,5-bisphosphate (PIP2) in platelet membranes of seven subjects (five male, two female; mean age=27.9+/-5.7 years), initially while they were unmedicated, and a second time after at least 21 days of lithium treatment (mean+/-SD=28.7+/-7.1 days). Results: The mean+/-SD values for PI were 5.63+/-2.25% and 5.21+/-1.06%: for PIP 0.68+/-0.20% and 0.55+/-0.11%: and for PIP, 0.60+/-0.21% and 0.38+/-0.15%. before and after lithium treatment, respectively. The decrease in PIP, values after lithium treatment was statistically significant (Wilcoxon signed ranks test, Z=-2.37, P=0.02). Conclusion: This longitudinal study suggests that therapeutic doses of lithium significantly decrease platelet membrane PIP2 levels in vivo in bipolar disorder subjects, which may be related to lithium's mechanism of action in bipolar disorder.